Anti-TPO

Thyroid peroxidase antibodies (TPOAb) are immune system proteins that mistakenly target thyroid peroxidase, an enzyme essential for producing thyroid hormones. This enzyme is responsible for key steps in hormone synthesis, including attaching iodine to the amino acid tyrosine, an essential process for forming thyroxine (T4) and triiodothyronine (T3). When your immune system produces TPO antibodies, it’s usually a sign that it’s attacking the thyroid gland itself, a hallmark of autoimmune thyroid diseases such as Hashimoto’s thyroiditis and, less commonly, Graves’ disease.

TPOAb isn’t just a diagnostic marker for autoimmune thyroid disease; it also helps predict who’s at higher risk of developing thyroid dysfunction, especially hypothyroidism. In people with mildly abnormal thyroid-stimulating hormone (TSH) levels, often called subclinical hypothyroidism, the presence of TPOAb makes it more likely that they’ll progress to overt, symptomatic hypothyroidism over time.

While high levels of TPOAb are nearly universal in Hashimoto’s thyroiditis, the presence of these antibodies can also be detected years before thyroid hormone levels begin to shift. That’s why TPOAb can be an early warning sign of thyroid dysfunction, even when TSH, T4, and T3 still look normal.

TPOAb is more common in women than men and tends to appear more often in younger adults. Lifestyle and physiological factors, like higher body mass index (BMI), smoking, and elevated TSH, also seem to increase the likelihood of having elevated TPO antibodies. According to population-based studies, about 12–13% of people are TPOAb-positive, though this varies by region and testing standards.

Role in Pregnancy

One of the most clinically significant roles for TPOAb testing is in pregnancy. Even in women whose thyroid hormone levels appear normal, the presence of TPOAb predicts a higher risk of complications such as premature delivery and miscarriage. The likely reason is that the immune attack on the thyroid limits its ability to respond to the increased hormonal demands of pregnancy, especially the early pregnancy surge in human chorionic gonadotropin (hCG), which normally stimulates the thyroid to make more hormone.

Interestingly, recent research suggests that even low-to-moderate levels of TPOAb—below current cutoffs used to define “positive”—may still increase the risk of premature delivery in a dose-dependent fashion. This challenges the conventional binary view of “positive” vs. “negative” and suggests we may need to rethink how these antibodies are interpreted in prenatal care.

Thyroid Cancer

Emerging research also links TPOAb to differentiated thyroid cancer (DTC), particularly in patients who already have nodules or goiter. People with TPOAb are more likely to have bilateral (both sides) or multifocal thyroid cancers, although the mechanism remains unclear. Some researchers believe that ongoing autoimmune inflammation may contribute to a microenvironment that promotes tumor development or detection.